P1725: OBSERVATIONAL STUDY TO EVALUATE PATIENT-REPORTED OUTCOMES IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
Authors: E. Urciuoli, E. Di Bona, S. Greve, A. De Vivo, S. Sica, R. Fontana, W. Barcellini, L. Marano, E. N. Oliva
Journal: HemaSphere (2022)

Background: Paroxysmal Nocturnal Hematuria (PNH) is a rare acquired hematopoietic stem cell disorder with non-specific clinical features and onset prevalent at young adult age. Main symptoms are fatigue (80%) and dyspnea (64%). Treatment for symptomatic and/or predominantly haemolytic PNH patients is associated with an improvement in survival and quality of life (QoL). To date, cancer-specific patient-reported outcome (PRO) measures (PROMS) have been used in PNH. A novel PNH-specific PROM, EORTC QLQ-AA/PNH, consisting of 54 items has undergone initial Phase 2-3 evaluation. We present preliminary results of the first 31 cases enrolled. Aims: The aim of this observational non-interventional prospective multicenter Italian study is to evaluate whether PROMs can identify patients’ biological response to treatment and factors associated with health-related QOL. The primary endpoint is differences in EORTC QLQ-C30 scores between patients with versus without hemolysis. Secondary endpoints include further validation of EORTC QLQ-AA/PNH Italian version, differences in scale scores between patients experiencing hemolysis versus those not experiencing hemolysis and factors associated with PROs by EORTC QLQ-AA/PNH. Methods: 110 adult patients age ≥ 18 years with PNH will be included. Exclusion criteria consists of bone marrow failure, history of treatment for cancer within the last 5 years and clinically significant comorbidities that impact PROs. Patients complete both PROMs on the day of visit to the clinic for the scheduled treatment and re-test after 2 weeks. For EORTC QLQ-AA/PNH higher scores identified higher impact or symptoms. Demographics and disease features are collected at baseline. Hemolysis is defined by a lactate dehydrogenase (LDH) ≥ 1.5 times upper limit of normal (ULN) at baseline. Results: Patient characteristics are shown in the Table 1. The EORTC QLQ-C30 scores did not distinguish patients with or without hemolysis, probably due to the small sample size. Baseline Global Function was good with median score 83 (IQR 50-100). Fatigue and dyspnea were not frequently reported with median scores 33 (IQR 11-33) and 0 (0-33), respectively. The EORTC QLQ-AA/PNH showed good reliability with Chronbach alpha standardized scores for all domains except Body Image (BI), Infections (IN) and Social Support (SS), confirmed at retest. There were strong correlations between the 2 questionnaires. QLQ-AA/PNH Cognitive Functioning (CF) median score was 0 (IQR 0-25), Emotional Functioning 20 (IQR 5-35), Fatigue (FA) 20 (IQR 10-30), Illness Intrusiveness (II) 11 (IQR 4-32), other symptoms (OS) 11 (0-21), Physical Functioning (PF) 17 (0-33), Role Functioning (RF) 14 (9-32), Stigmatisation (ST) 12 (0-25) and Fear of Progression (PAF) 123 (4-29). Hemoglobin levels correlated with QLQ C30 physical function (R=0.505, P=0.006), role function (R=0.450, P= 0.014), Fatigue (R=-0.520, P=0.004), Dyspnea (R=-0.410, P=0.027) and Pain (R0-0.409, P0 0.028). They correlated with EORTC QLQ-AA/PNH PF (R=0.499, P=0.006), ST (R=0.395, P=0.034) and FA (r=-0.517, p=0.004). Image:Summary/Conclusion: The preliminary analysis confirms the validity of the EORTC QLQ-AA/PNH as a PROM for PNH. Hemoglobin is an important factor which correlates with many PRO domains. Further analyses at study completion will inform on the impact of PNH in patients’ lives.